(±)-a-[(tert-Butylamino)methyl]-3,5-dihydroxybenzyl alcohol sulfate (2:1)(salt) [23031-32-5].
»Terbutaline Sulfate contains not less than 98.0percent and not more than 101.0percent of (C12H19NO3)2·H2SO4,calculated on the dried basis.
Packaging and storage Preserve in well-closed,light-resistant containers,at controlled room temperature.
USP Reference standards á11ñ USP Terbutaline Sulfate RS.USP Terbutaline Sulfate Related Compound A RS.
A: Infrared Absorption á197Kñ.
B: The retention time of the major peak in the chromatogram of the Assay preparationcorresponds to that in the chromatogram of the Standard preparation,as obtained in the Assay.
Acidity Dissolve 0.20g in 10mLof carbon dioxide-free water,and titrate with 0.020Nsodium hydroxide from a microburet to a pHof about 6,determining the endpoint potentiometrically,using a calomel-glass electrode system:not more than 0.50mLof 0.020Nsodium hydroxide is required (0.3%as acetic acid).
Loss on drying á731ñ Dry it at 105for 3hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ: not more than 0.2%.
Heavy metals,Method IIá231ñ: 0.0025%.
Ion-pair solution,Mobile phase,System suitability solution,and Chromatographic system Proceed as directed in the Assay.
Standard solution Dissolve an accurately weighed quantity of USP Terbutaline Sulfate RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 3µg per mL.
Test solution Use the Assay preparation.
Procedure Separately inject equal volumes (about 20µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the peak responses.Calculate the percentage of each impurity,if present,in the portion of Terbutaline Sulfate taken by the formula:
5000(C/W)(ri/rS),in which Cis the concentration,in mg per mL,of USP Terbutaline Sulfate RSin the Standard solution;Wis the weight,in mg,of Terbutaline Sulfate taken to prepare the Test solution;riis the peak response for each impurity obtained from the Test solution;and rSis the terbutaline peak response obtained from the Standard solution:the sum of all impurities is not more than 1.0%.
Organic volatile impurities,Method Iá467ñ: meets the requirements.
Ion-pair solution Transfer 3.15g of ammonium formate to a 1000-mLvolumetric flask,dissolve in about 900mLof water,adjust the solution with formic acid to a pHof about 3.0,add 5.49g of sodium 1-hexanesulfonate,dilute with water to volume,and mix.
Mobile phase Prepare a filtered and degassed mixture of Ion-pair solutionand methanol (77:23).Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
System suitability solution Dissolve accurately weighed quantities of USP Terbutaline Sulfate RSand USP Terbutaline Related Compound A RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having known concentrations of 1.0mg per mLand 0.4mg per mL,respectively.
Standard preparation Dissolve an accurately weighed quantity of USP Terbutaline Sulfate RSin Mobile phase,and dilute quantitatively,and stepwise if necessary,with Mobile phaseto obtain a solution having a known concentration of about 1.0mg per mL.
Assay preparation Transfer about 50mg of Terbutaline Sulfate,accurately weighed,to a 50-mLvolumetric flask,dissolve in and dilute with Mobile phaseto volume,and mix.
Chromatographic system (see Chromatography á621ñ) The liquid chromatograph is equipped with a 276-nm detector and a 4.6-mm ×15-cm column that contains 5-µm packing L1.The flow rate is about 1mLper minute.Chromatograph the System suitability solution,and record the peak responses as directed for Procedure:the relative retention times for terbutaline related compound Aand terbutaline are 0.9and 1.0,respectively;the resolution,R,between terbutaline related compound Aand terbutaline is not less than 2.0;the column efficiency is not less than 1500theoretical plates;the tailing factor for the terbutaline peak is not more than 2.0;and the relative standard deviation for replicate injections determined from the terbutaline peak is not more than 2.0%.
Procedure Separately inject equal volumes (about 20µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of (C12H19NO3)2·H2SO4in the portion of Terbutaline Sulfate taken by the formula:
50C(rU/rS),in which Cis the concentration,in mg per mL,of USP Terbutaline Sulfate RSin the Standard preparation;and rUand rSare the peak responses obtained from the Assay preparationand the Standard preparation,respectively.
Auxiliary Information Staff Liaison:Karen A Russo,Ph.D.,Scientist
Expert Committee:(PA1)Pharmaceutical Analysis 1
USP28NF23Page 1869Pharmacopeial Forum:Volume No.29(5)Page 1585